Journal of Materials Chemistry B
·
2024
·Vol. 12
·期 4
·1007-1021
·
IF 6.1
Qixin Zhou,Xiaodan Li,Nan Gao,Guixia Ling,Peng Zhang
Diabetic wounds in a state of high glucose are refractory to treatment and healing, especially if they are infected with bacteria. Herein, a novel nanocomposite (CIP/GOx@ZIF-8) was synthesized by loading ciprofloxacin hydrochloride (CIP) and glucose oxidase (GOx) into zeolitic imidazole framework-8 (ZIF-8) that exhibited good glucose sensitivity and catalytic activity. The high glucose in diabetic wounds could be decomposed into hydrogen peroxide (H2O2) and gluconic acid via the catalysis of GOx, which further destroyed CIP/GOx@ZIF-8 to release Zn2+ and cargos. The combination of glucose starvation, Zn2+, H2O2 and CIP could elevate the antibacterial effect and reduce bacterial resistance. Subsequently, the nanocomposite was fabricated into dissolving microneedles (CIP/GOx@ZIF-8 MNs) using polyvinylpyrrolidone (PVP). The microneedles exhibited good mechanical strength, puncture performance, dissolving performance, glucose responsiveness, antibacterial performance and biocompatibility. For in vivo wound healing, CIP/GOx@ZIF-8 MNs with good biosafety facilitated neovascularization and collagen deposition as well as reduced inflammation, and the wounds were almost healed after treatment. This multimodal therapeutic strategy is created to provide a unique treatment for infected diabetic wounds.
研究领域:
材料科学
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纳米技术
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生物医学工程
·
药学
·
伤口愈合
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Kunzhao Huang,Xiaoyuan Yi,Huaying Xie,Jianzhang Luo,Qingyu Zeng,Feifei He,Liyan Wang
Purpose Ferroptosis is a regulated form of cell death characterized by iron-dependent accumulation of associated lipid peroxides (LPO), which can induce cell death when a certain level is reached. However, the extremely complex tumor microenvironment (TME) has the characteristics of antioxidant, even if it induces ferroptosis of tumor cells, its killing effect on tumor cells is still very limited. To solve this problem, we constructed a novel nanomaterials (GOx/EC@Fe3O4@CCM). We evaluated the anticancer effect of this nanomaterial in inhibiting tumor growth through comprehensive in vitro and in vivo experiments.Methods We successfully synthesized GOx/EC@Fe3O4 by one-pan synthesis method, then coated the Hepatocellular carcinoma cell membrane on its surface by co-extrusion technology, and finally synthesized the GOx/EC@Fe3O4@CCM nanoplatforms. We characterized the compounds in terms of morphology, particle size, and Zeta potential. In addition, we also studied the anti-tumor effect of GOx/EC@Fe3O4@CCM nanoplatforms from the following aspects, including the performance test of the nanoplatform, the intracellular effect of the nanoplatform, the anti-tumor effect in vitro, the intracellular ROS analysis, the intracellular effect of EC, and the anti-tumor effect in vivo.Results The iron-based carriers in GOx/EC@Fe3O4@CCM nanoplatforms are released and produce ferrous ions (Fe2+) in an acidic environment. Due to the limitation of the endogenous level of hydrogen peroxide (H2O2), we introduced GOx into the TME or tumor cells. Under the catalysis of GOx, glucose reacted rapidly to produce a large amount of H2O2, which then combined with Fe2+ to produce a large number of Hydroxyl radical (·OH). Its toxicity leads to dysfunction of cell membrane and organelles, and then causes cell damage. EC inhibits Nuclear factor erythroid 2-related factor 2 (Nrf2) in cancer cells, which effectively down-regulates downstream gene products, including NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HMOX1). A series of chain reactions reduce the escape effect of oxidative stress (OS) and effectively maintain a high level of intracellular oxidation. Furthermore, it induces sustained and intense ferroptosis in tumor cells. Finally, the use of cancer cell membrane modified nanoplatforms due to the homology of membrane protein components improves the tumor cell targeting of the nanoplatforms, showing significant tumor cell inhibition and killing effect in vivo.Conclusion The results showed that the GOx/EC@Fe3O4@CCM nanoplatforms successfully induced significant ferroptosis of Hepatocellular carcinoma cells through a cascade effect, and finally effectively promoted cancer cell regression.
研究领域:
癌症研究
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纳米技术
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生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Yinghui Xu,Jiayi Bian,Xin Liu,Zhengzheng Qian,Minghao Sun,Cheng Zhang,Ruiyang Pan,Qitong Li,Changrui Sun,Bin Lin,Kun Peng,Nan Lu,Xikuang Yao,Wenpei Fan
Photothermal therapy (PTT) combined with chemodynamic therapy (CDT) presents an appealing complementary anti-tumor strategy, wherein PTT accelerates the production of reactive oxygen species (ROS) in CDT and CDT eliminates residual tumor tissues that survive from PTT treatment. However, nanomaterials utilized in PTT/CDT are limited by non-specific damage to the entire organism. Herein, a glucose-responsive enzymatic Fe@HRP-ABTS/GOx nanodot is judiciously designed for tumor-specific PTT/CDT via a simple and clean protein-templated biomimetic mineralization synthesis. By oxidizing glucose in tumor cells, glucose oxidase (GOx) activates glucose-responsive tumor therapy and increases the concentration of H 2 O 2 at the tumor site. More importantly, the self-supplied peroxide hydrogen (H 2 O 2 ) can convert ABTS (2,2′-Hydrazine-bis(3-ethylbenzothiazoline-6-sulfonic acid) diamine salt) into oxidized ABTS (oxABTS) through horseradish peroxidase (HRP) catalysis for PTT and photoacoustic (PA) imaging. Furthermore, the Fe 2+ arising from the reduction of Fe 3+ by overexpressed GSH reacts with H 2 O 2 to generate intensely reactive •OH through the Fenton reaction, concurrently depleting GSH and inducing efficient tumor CDT. The in vitro and in vivo experiments demonstrate superior cancer cell killing and tumor eradication effect of Fe@HRP-ABTS/GOx nanodot under near-infrared (NIR) laser irradiation. Collectively, the nanodots provide mutually reinforcing catalytic PTT/CDT anti-tumor strategies for treating liver cancer and potentially other malignancies. Statement of significance Combinatorial antitumor therapy with nanomedicines presents great prospects for development. However, the limitation of non-specific damage to normal tissues hinders its further clinical application. In this work, we fabricated tumor-selective biomimetic Fe@HRP-ABTS/GOx nanodots for H 2 O 2 self-supplied catalytic photothermal/chemodynamic therapy of tumors. The biomimetic synthesis strategy provides the nanodots with enzymatic activity in response to glucose to produce H 2 O 2 . The self-supplied H 2 O 2 initiates photothermal therapy with oxidized ABTS and enhances chemodynamic therapy through simultaneous •OH generation and GSH depletion. Our work provides a new paradigm for developing tumor-selective catalytic nanomedicines and will guide further clinical translation of the enzymatic biomimetic synthesis strategy.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Guiqiang Qi,Guangyue Shi,Shengchao Wang,Haifeng Hu,Zhichen Zhang,Qiangqiang Yin,Zhongtao Li,Liguo Hao
Introduction This study developed a pancreatic cancer targeted drug delivery system that responds to changes in acidity. The system was based on iron oxide core-shell magnetic mesoporous silica nanoparticles (M-MSNs) to treat pancreatic cancer through combined chemotherapy and starvation therapy.Methods Glucose oxidase (Gox) was coupled to the cancer cell surface to reduce glucose availability for cancer cells, exacerbating the heterogeneity of the tumor microenvironment. Reduced pH accelerated the depolymerization of pH-sensitive polydopamine (PDA), thereby controlling the spatial distribution of Gox and release of doxorubicin (DOX) within tumor cells.Results Characterization results showed the successful synthesis of DG@M-MSN-PDA-PEG-FA (DG@NPs) with a diameter of 66.02 ± 3.6 nm. In vitro data indicated DG@NPs were highly effective and stable with good cellular uptake shown by confocal laser scanning microscopy (CLSM). DG@NPs exhibited high cytotoxicity and induced apoptosis. Additionally, in vivo experiments confirmed DG@NPs effectively inhibited tumor growth in nude mice with good biosafety. The combination of starvation therapy and chemotherapy facilitated drug release, suggesting DG@NPs as a novel drug delivery system for pancreatic cancer treatment.Conclusion This study successfully constructed a doxorubicin release system responsive to acidity changes for targeted delivery in pancreatic cancer, providing a new strategy for combination therapy.
研究领域:
药剂学
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2020
·
IF 3.99
Jiawei Li,Tong Li,Dmitry Gorin,Yuri Kotelevtsev,Zhengwei Mao,Weijun Tong
Cascade nanoreactors (NRs) which can be activated in tumor microenvironment and catalyze the local substance to toxic species for killing cancer cells is an appealing emerging agent for cancer treatment in recent years. Peroxidase-like nanozymes are often integrated into such kind of systems for cancer therapy. In this study, magnetic metal-organic framework (MOF: zeolitic imidazolate framework 8, ZIF-8) nanoparticles (NPs) with ferrimagnetic structures inside are fabricated via the mineralization of iron during the growth of ZIF-8. The Fe-base magnetic structures can serve as peroxidase-like nanozyme. After the loading of GOx on the magnetic MOF NPs, magnetic cascade MOF/enzyme hybrid NRs ( [email protected] @GOx NRs) are successfully constructed. In the presence of glucose, the NRs can perform high cascade reaction activity to produce hydroxyl radicals (•OH) under mild acidic condition at physiological temperature. The NRs can be more internalized by cancer cells under a magnetic field and take advantage of acidic environment in lysosomes to produce high toxic •OH by cascade reaction to kill cancer cells. Magnetic targeting to kill cancer cells at the specified location can be achieved by applying a magnetic field to the targeted area and then damage to normal cells will be minimized.
研究领域:
纳米技术
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癌症研究
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生物化学
·
材料科学
✓ 已验证
DOI
高影响因子
Advanced Therapeutics
·
2023
·Vol. 6
·期 4
·2200304
·
IF 4.6
Dan Zhao,Min Wu,Yanan Tian,Lu Gao,Fu Wang
With the advantages of ferroptosis therapy (FT) in solving the apoptotic resistance of tumors, a smart strategy based on the combination of glucose oxidase (GOx) and ferroptosis-inducing nanoagents is proposed to boost the FT. However, most of the nanoagents remain limited in complex synthesis, poor targeting specificity, and unclarified biological mechanisms. Herein, a multifunctional nanoplatform based on fluorescent apoferritin-gold nanoclusters combined with GOx (AFt-AuNCs@GOx) is designed for tumor-targeted imaging and FT. The results show that AFt-AuNCs@GOx catalyze the generation of toxic ·OH from H 2 O 2 supplied by GOx. Consequently, AFt-AuNCs@GOx induce the enhanced ferroptosis effect in 4T1 cells. Additionally, the transcriptome assay of 4T1 cells identifies the differential expression genes related to ferroptosis process after AFt-AuNCs@GOx treatment. Moreover, with the merit of intrinsic fluorescence, the biodistribution both in vitro and in vivo of AFt-AuNCs@GOx can be effectively visualized. In vivo evidences reveal that AFt-AuNCs@GOx have the desired efficacy of FT and excellent biosafety. Overall, the AFt-AuNCs@GOx nanoplatform offer remarkable advantages in simple architecture, fluorescent imaging, precise targeting, and tumor inhibition. The exploration of the ferroptosis effect and biological mechanisms of AFt-AuNCs@GOx, as well as its application in tumor therapy, can introduce a new insight into the field of ferroptotic nanomedicine.
研究领域:
纳米技术
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癌症治疗
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分子生物学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2022
·
IF 5.395
Gaoqian Zhao,Yan Jin,Shutao Gao,Tingshan Xiao,Miao Fan,Dandan Liu,Jinchao Zhang,Zhenhua Li,Xiaohan Zhou,Huifang Liu
The low sensitivity of hypoxic regions in solid tumors to radiotherapy and chemotherapy remains a major obstacle to cancer treatment. By taking advantage of hypoxic-activated prodrugs, tirapazamine (TPZ), generating cytotoxic reductive products and the glucose oxidase (GOx)-based glucose oxidation reaction, we designed a nanodrug-loading system that combined TPZ-induced chemotherapy with GOx-mediated cancer-orchestrated starvation therapy and cancer oxidation therapy. In this work, we first prepared mesoporous silica (MSN) loaded with TPZ. Then, in order to prevent the leakage of TPZ in advance, the surface was coated with a layer of carMOF formed by Fe3+ and carbenicillin (car), and GOx was adsorbed on the outermost layer to form the final nanosystem MSN-TPZ@carMOF-GOx (MT@c-G). GOx could effectively consume oxygen and catalyzed glucose into gluconic acid and hydrogen peroxide. First, the generated gluconic acid lowered the pH of tumor tissues, promoted the decomposition of carMOF, and released TPZ. Second, oxygen consumption could improve the degree of hypoxia in tumor tissues, so that enhanced the activity of TPZ. Furthermore, GOx could generate cancer-orchestrated starvation/oxidation therapy. Therefore, our study provided a new strategy that TPZ combined with GOx achieved starvation/oxidation/chemotherapy for enhancing anticancer effects in hypoxic regions.
研究领域:
癌症研究
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药物科学
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纳米医学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Nana Li,Liangqiang Chen,Wanqiu Huang,Mengdi Hao,Huabin Tu,Hao Shen,Fan Yang,Shaoning Yu
As one of the most important industrial enzymes, α-amylase is widely used in food processing, such as starch sugar and fermentation, bringing high added value to industry of more than a trillion dollars. We developed a multi-enzyme system (Glu&Gox@Cu-MOF-74) prepared by embedding α-glucosidase (Glu) and glucose oxidase (Gox) into the biomimetic metal-organic framework Cu-MOF-74 using in situ encapsulation within 15 min at room temperature for efficient and sensitive detection of α-amylase activity. Benefitting from the remarkable peroxidase-mimicking property and rigid skeleton of Cu-MOF-74, the biocatalytic platform exhibited excellent cascade activity and tolerance in various extremely harsh environments compared to natural enzymes. On this basis, a cascade biocatalytic platform was constructed for the detection of α-amylase activity with wide linear range (5–100 U/L) and low limit of detection (1.45 U/L). The colorimetric cascade scheme is important for the sensitive and selective determination of α-amylase in complex fermentation samples, and the detection time is short (∼0.5 h). This work provides new ideas for the detection of α-amylase based on the cascade amplification method.
研究领域:
生物化学
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生物技术
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2019
·
IF 6.393
Jiaojiao Zhou,Wenjing Wang,Shuojun Li,Axiu Nie,Zhiyong Song,Mohamed F. Foda,Zhicheng Lu,Ling Zhao,Heyou Han
An innovative fluorescent and colorimetric dual-mode strategy based on Y-shaped DNA was proposed for the detection of rabies virus oligonucleotide. The cascade assembly of hairpin probes was initiated by the target, leading to the formation of Y-shaped DNA accompanied by freeing target to catalyze the next assembly process. The fluorescence recovery of the fluorophore FAM was accompanied by opening of hairpin probe. A colorimetric signal was generated by the proximity of glucose oxidase (GOx) and horseradish peroxidase (HRP), which was reflected by enhanced catalytic capability to TMB. Using this method, target DNA can be detected with a wide linear range from 0.1 to 6 nM with a detection limit of 15 pM, and from 0.5 to 60 nM with a detection limit of 60 pM for fluorescent and colorimetric readout, respectively. Moreover, the dual-mode detection strategy exhibited excellent selectivity towards the target compared with interference oligonucleotides. In addition, recoveries ranging from 96.0% to 106% with RSD values varying from 3.2% to 5.4%, and from 91.0% to 102% with RSD values varying from 3.3% to 7.1% for fluorescent and colorimetric studies, respectively, were obtained in diluted cerebrospinal fluid samples. The proposed dual-mode sensor is easy to operate with excellent detection performance. It would be superior to single mode detection and more practicable for quantitative detection of nucleic acid-related biomarkers due to the self-correction capability.
研究领域:
生物化学
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分子生物学
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分析化学
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病毒学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Fan Yang,Rui Shu,Bin Li,Wenyu Dai,Wanxi Chen,Jiamin Sun,Ding Bai,Weizhong Yang,Yi Deng
Persistent activation of NLRP3 inflammasomes in infectious diabetic wounds lead to uncontrolled inflammation. Hydrogen sulfide (H 2 S) gas therapy shows promise in inhibiting inflammasomes. However, on-demand delivery of H 2 S is challenging, as its biological characteristics are Janus-faced. Herein, we present the anti-inflammasome bio-heterojunction (AI-bioHJ), comprising FeS, Cu 2 O, and glucose oxidase (GOx), capable of H 2 S gas evolution and in situ self-transformation to accelerate diabetic wound healing. In this system, AI-bioHJ release H 2 S to inhibit NLRP3 inflammasomes and recycle excess H 2 S through a reaction between Cu 2 O and H 2 S, maintaining a low H 2 S concentration while upgrading type I FeS/Cu 2 O to Z-scheme FeS/CuS bioHJ, and markedly enhancing phototherapy. Additionally, GOx depletes local glucose to generate H 2 O 2 , promoting Fenton-like reactions and rapid pathogenic elimination. In vivo and in vitro assessments confirm AI-bioHJ effectively eliminate pathogen, inhibit inflammasomes and facilitate diabetic wound healing. Transcriptome analysis indicates that the FoxO–autophagy axis may mediate the anti-inflammasome effects. Altogether, our work provides enlightenments into programmed H 2 S-releasing bioHJ for remedying diabetic wounds.
研究领域:
生物材料
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伤口愈合
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炎症
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气体疗法
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纳米技术
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Junhao Zhang,Nan Chen,Luping Ren,Lei Nie,Khaydar E. Yunusov,Uladzislau E. Aharodnikau,Sergey O. Solomevich,Yanfang Sun,Guohua Jiang
In this study, a multifunctional Cu-doped CaO 2 nanoreactor loaded with GOx and camouflaged with a folic acid-modified cell membrane was developed for breast cancer treatment. The as-developed composite nanoreactor showed a synergistic effect on calcium overload to damage mitochondria, thus killing tumor cells to achieve ion interference therapy (IIT). The loaded GOx could deplete glucose to “starve” tumor cells. The H 2 O 2 released by CaO 2 decomposition and enzyme catalytic reactions from GOx could not only be highly toxic in the tumor microenvironment but also enhance the efficiency of chemodynamic therapy (CDT) with Cu 2+ . The red blood cell membranes modified by folic acid achieved a combination of active targeting and passive targeting, thereby enhancing the targeting ability of the as-prepared multifunctional composite nanoreactor and prolonging its retention time at the tumor sites for more than 48 h.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Lu Zhang,Huan Shen,Tingting Liu,Bin Li,Xi Chen,Hong Wang,Chenyang He,Yang Liu,Gang Cao,Shuo Yu
Chemodynamic therapy (CDT) has garnered significant attention in the field of tumor therapy due to its ability to convert overexpressed hydrogen peroxide (H 2 O 2 ) in tumors into highly toxic hydroxyl radicals (•OH) through metal ion-mediated catalysis. However, the effectiveness of CDT is hindered by low catalyst efficiency, insufficient intra-tumor H 2 O 2 level, and excessive glutathione (GSH). In this study, a pH/GSH dual responsive bimetallic nanocatalytic system (CuFeMOF@GOx@Mem) is developed by modifying red blood cell membranes onto glucose oxidase (GOx)-loaded Fe-Cu bimetallic MOFs, enhancing the efficacy of CDT through a triple-enhanced way by H 2 O 2 self-supply, catalysts self-cycling, and GSH self-elimination. Upon accumulation in tumor tissues facilitated by the red blood cell membrane, the GOx initiates a reaction with glucose to generate H 2 O 2 and gluconic acid in situ. Subsequently, the reduced pH triggers the release of Fe 3+ and Cu 2+ from CuFeMOF@GOx@Mem, which is immediately turned into Fe 2+ and Cu + by GSH, activating the Fe 2+ -mediated Fenton reaction. More importantly, Cu + can also act as an accelerator of Fe 3+ /Fe 2+ conversion, meanwhile, the generated Cu 2+ can be further reduced to Cu + by GSH. Consequently, sustained accumulation of H 2 O 2 and Fe 2+ as well as sustained elimination of GSH are achieved simultaneously, providing a unique approach for improving the anti-tumor ability of CDT.
研究领域:
癌症治疗
·
纳米医学
·
生物化学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）